Current Gene Therapy[JOURNAL]
Sun
200 papers
Harnessing Nanotechnology and Gene Editing for Cancer Therapy: A Synergistic Approach to Precision Medicine.
Goel A, Saraswat I, Sharma S … +1 more , Joshi R
Curr Gene Ther · 2025 Aug · PMID 40760752 · Publisher ↗
The fusion of nanotechnology with gene editing promises a revolutionary strategy in combating cancer, providing the possibility of precise and focused treatments. This review examines the synergistic integration of these...
The fusion of nanotechnology with gene editing promises a revolutionary strategy in combating cancer, providing the possibility of precise and focused treatments. This review examines the synergistic integration of these two potent technologies, specifically emphasising their combined effectiveness in oncological therapies. Nanotechnology offers a flexible framework for administering gene-editing tools, improving their accuracy, and reducing unintended side effects, all of which are significant obstacles in existing cancer treatments. Nanoparticles can improve the effectiveness of therapies, lower the risk of systemic toxicity, and allow the simultaneous manipulation of many genetic pathways involved in cancer growth by delivering CRISPR-Cas9 and other gene-editing systems directly to tumour sites. We conduct a thorough analysis of recent progress in this burgeoning field, emphasising significant advancements in the design of nanoparticles and gene-editing techniques that propel the development of next-generation cancer medicines. In addition, we address the present obstacles and constraints, such as the effectiveness of delivery, apprehensions over safety, and regulatory obstacles, while suggesting potential areas of future research to surmount these barriers. This study thoroughly examines the promise of nano-precision gene editing as a transformative approach to cancer treatment by incorporating findings from recent clinical trials and case studies. By highlighting recent clinical advancements and emerging innovations, this review underscores the potential of nano-precision gene editing as a groundbreaking approach in next-generation cancer therapy.
PAK1 Signaling in Cancer: Multifaceted Roles and Therapeutic Implications.
Meman F, Tandel D, Navale A
Curr Gene Ther · 2025 Aug · PMID 40760751 · Publisher ↗
PAK1, a serine-threonine kinase, acts as an effector of Rac, Ras, and CDC42, which are pivotal in oncogenic signaling pathways. Its involvement spans critical cellular processes like cell cycle regulation, angiogenesis,...
PAK1, a serine-threonine kinase, acts as an effector of Rac, Ras, and CDC42, which are pivotal in oncogenic signaling pathways. Its involvement spans critical cellular processes like cell cycle regulation, angiogenesis, and metastasis. PAK1 also influences therapeutic resistance mechanisms in various cancers. Serving as a linchpin in diverse signaling pathways pivotal to cancer progression, PAK1 positions itself as a promising therapeutic target. The comprehensive understanding of PAK1's roles in cancer biology underscores its potential for targeted interventions and offers prospects for improved cancer diagnostics and treatment strategies.
Pathogens Association with Alzheimer Disease: Emerging Concepts and New Perspectives.
Agarwal U, Tonk RK, Verma S
Curr Gene Ther · 2026 · PMID 40735980 · Publisher ↗
Alzheimer's Disease (AD) represents a significant global health challenge, distinguished by a complex pathology that involves the accumulation of abnormal proteins in the brain, leading to neuronal loss and brain atrophy...
Alzheimer's Disease (AD) represents a significant global health challenge, distinguished by a complex pathology that involves the accumulation of abnormal proteins in the brain, leading to neuronal loss and brain atrophy. Recent research has indicated a potential association between various pathogens and the development of AD, suggesting that infectious pathogens may play a role in its pathology. The study focuses on the exploration of pathogens linked to AD. It aims to enhance the understanding of the disease's etiopathogenesis, which refers to the causes and development of the condition. The findings from this analysis have the potential to contribute to improved diagnostic methods and treatment strategies for AD. Overall, the manuscript highlights the importance of exploring infectious pathogens relating to neurodegenerative disorders. This comprehensive literature review was conducted using databases such as PubMed and Scopus, focusing on research published up to March 2025..Articles were searched based on keywords related to reviews and research exploring the association/link between different pathogens and AD, emerging interventions, preventive strategies, and limitations in study design. This study indicates that various viruses, bacteria, and fungi are significant contributors to the condition, while parasites and prions play a lesser role. Notably, the variability in pathogen species among patients could provide insights into the evolution and severity of clinical symptoms associated with the disease. Additionally, some studies propose that after modification, certain fungi may actually reduce the amyloid burden in Alzheimer's patients. However, it is crucial to emphasize that there is currently no definitive evidence supporting the notion that treating infections alone can prevent or cure AD. The prevention and treatment of pathogens, including viruses, bacteria, and fungi, as well as infectious prions, may play a significant role in reducing the risk of AD. Effective management of these pathogens can help to control and prevent further damage in individuals who have already been diagnosed with AD. There is a pressing need for additional pre-clinical and clinical research to deepen the understanding of the pathophysiological connections between pathogens and AD.
Association of KIM-1 (HAVCR1) Expression with the Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.
Vlachostergios PJ, Karathanasis A, Karasavvidou F … +1 more , Tzortzis V
Curr Gene Ther · 2026 · PMID 40735979 · Publisher ↗
INTRODUCTION: Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed in the proximal tubules and encoded by the hepatitis A virus cellular receptor 1 (HAVCR1) gene. It is also expressed in renal cell c...
INTRODUCTION: Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed in the proximal tubules and encoded by the hepatitis A virus cellular receptor 1 (HAVCR1) gene. It is also expressed in renal cell carcinoma (RCC). OBJECTIVE: This study examined the immune landscape of clear cell RCC in association with HAVCR1 expression. METHODS: Next-generation sequencing (NGS) data from ccRCC tumor samples of patients from The Cancer Genome Atlas (TCGA) were interrogated for enrichment of immune infiltrates and checkpoints in tumors harboring high HAVCR1 mRNA expression or/and amplification. RESULTS: HAVCR1 mRNA expression was positively associated with presence of CD8 (r = 0.254, p = 3.03 x 10) and CD4 T-cells (r = 0.329, p = 3.98 x 10), while it was negatively associated with T-regulatory (T-regs) (r = ̶ 0.2, p = 1.47 x 10) and myeloid-derived suppressor cells (MDSCs) (r = ̶.0.285, p = 4.92 x 10). HAVCR1 amplification was also associated with CD8 (p = 0.0019), CD4 T cells (p = 0.0002) while expression of HAVCR1 gene was positively associated with immune checkpoints PD-L1 (CD274) (r = 0.331, p = 4.64 x 10) and CTLA4 mRNA expression (r = 0.085, p = 0.05). HAVCR1 transcript levels were directly correlated with those of Polybromo-1 (PBRM1) (r = 0.276, p = 9.36 x 10) while inversely related with BRCA-associated protein 1 (BAP1) gene expression (r = ̶ 0.134, p = 1.94 x 10). DISCUSSION: The study reveals that high HAVCR1 (KIM-1) expression in clear cell RCC is associated with a distinct immune profile characterized by increased CD8/CD4 T-cell infiltration and immune checkpoint expression, suggesting a potential role in predicting immunotherapy response, though the observational nature and reliance on TCGA data limit causal inference. CONCLUSIONS: Collectively, a potential immune-regulatory role of KIM-1 in clear cell RCC is implicated. This could be exploited for predicting benefit from adjuvant immunotherapy.
DrugSurvPlot: A Novel Web-Based Platform Harnessing Drug Sensitivity Scores as Molecular Biomarkers for Pan-Cancer Survival Prognosis.
Shi Y, Shen Q, Jiang A … +5 more , Yang H, Li K, Zhang J, Lin A, Luo P
Curr Gene Ther · 2026 · PMID 40734432 · Publisher ↗
BACKGROUND: Using predicted drug sensitivity scores as survival biomarkers may improve precision medicine and overcome the limitations of genomically guided approaches in clinical trials. METHODS: Pan-Cancer Drug Sensiti...
BACKGROUND: Using predicted drug sensitivity scores as survival biomarkers may improve precision medicine and overcome the limitations of genomically guided approaches in clinical trials. METHODS: Pan-Cancer Drug Sensitivity Score Survival Analysis (DrugSurvPlot) is an interactive, login-free web analyzer built with R (v4.3.1), leveraging the Shiny package for interface/server logic, the DT package for data table queries/downloads, and the survival package for survival analysis. Data preprocessing was performed using OncoPredict, enabling users to export processed tables and results. RESULTS: DrugSurvPlot integrates 189 GEO datasets (including 10 immune checkpoint inhibitor treatment datasets) and 33 TCGA datasets, totaling 85,531 records across 52 cancer types and 13 survival status data types, while incorporating 198 anticancer drugs from GDSC2. This tool supports two cutoff strategies for drug sensitivity scores, offers advanced survival analysis methods, and enables customizable high-definition visualization of results. DISCUSSION: DrugSurvPlot represents a significant advancement in computational oncology by establishing predicted drug sensitivity scores as novel prognostic biomarkers for tumor survival analysis. This interactive platform integrates comprehensive datasets spanning 198 anticancer drugs and 52 cancer types, while providing researchers with intuitive tools for generating publication-ready Kaplan-Meier analyses. Current limitations in drug repertoire coverage and dataset diversity will be addressed through ongoing expansion of pharmacological databases and incorporation of emerging data modalities, including single-cell transcriptomics. CONCLUSIONS: In summary, DrugSurvPlot offers a no-code platform with comprehensive datasets, diverse cancer coverage, and customizable survival analysis, addressing critical research gaps. Continuous enhancements will improve predictive accuracy and clinical utility, establishing it as an evolving powerhouse in drug-survival investigations.
Genomic Medicine: A Critical Review of its Impact on Diagnosing and Treating Genetic Disorders.
Sundaram V, Rengarajan SK, Manikandan S … +4 more , Anbalagan S, Sivakumar VL, Packiyam T, Chopra H
Curr Gene Ther · 2025 Jul · PMID 40698698 · Publisher ↗
Genomic medicine is revolutionizing genetic disease diagnosis and therapy; has a major impact on clinical practice, particularly in diagnosis and treatment. In addition, next-generation sequencing (NGS) has transformed d...
Genomic medicine is revolutionizing genetic disease diagnosis and therapy; has a major impact on clinical practice, particularly in diagnosis and treatment. In addition, next-generation sequencing (NGS) has transformed diagnostics. These advances have made genome profiling costeffective and fast, helping us find pathogenic variations that cause a variety of genetic illnesses. Given its influence on diagnostic methods, NGS mutation detection accuracy and reliability must be assessed. In therapeutics, genomic medicine has introduced precision methods. CRISPR-Cas9 gene editing, and new RNA-based therapies are being evaluated for the treatment of genetic mutations Pharmacogenomics' capacity to customize medication regimens to genetic profiles, optimizing therapeutic results while minimizing side effects, is also evaluated. Although genetic medicine has transformational promise, its widespread acceptance is difficult. Obtaining widespread acceptance of genetic medicine is difficult because of worries around ethical implications, privacy problems, and the possibility for genetic information to be misused. Ethics and privacy issues surrounding genetic information usage require considerable thought. Genomic data integration into clinical practice requires robust regulatory frameworks. The influence of NGS technology and precision treatments on genetic disease diagnosis and therapy is significant. This review emphasizes the importance of assessing diagnostic tools, comprehending novel therapy modalities, and addressing ethical and regulatory issues to enable responsible and successful clinical integration.
The Mitochondrial Deoxyribonucleic Acid Puzzle: Controversies, Challenges, and Critical Perspectives - A Narrative Review.
Kumar N, Mangla M
Curr Gene Ther · 2025 Jul · PMID 40696553 · Publisher ↗
Human mitochondrial DNA (mtDNA) stands at the nexus of scientific intrigue and controversy, owing to its distinctive genetic features and indispensable role in cellular energy dynamics. This narrative review explores the...
Human mitochondrial DNA (mtDNA) stands at the nexus of scientific intrigue and controversy, owing to its distinctive genetic features and indispensable role in cellular energy dynamics. This narrative review explores the complexities, controversies, and key issues in current research on human mtDNA. A comprehensive search on literature spanning from January 2000 to January 2025 was conducted across electronic databases including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "mitochondrial DNA," "mtDNA mutations," "mtDNA inheritance," "mitochondrial genetics," "mitochondrial diseases," and "future perspectives of mtDNA" were used to identify relevant studies published in peer-reviewed journals, books, and reputable conference proceedings. Articles selected for inclusion were limited to those written in English and focused on human mtDNA research. Review articles, original research papers, metaanalyses, and authoritative texts were prioritized. Information extracted from selected studies was synthesized to provide a comprehensive overview. The synthesized data were critically analyzed to highlight emerging trends, unresolved controversies, and future research directions in the field of mtDNA research. Decoding the complexities of human mtDNA offers profound insights into fundamental biological processes and evolutionary history. This review emphasizes the ongoing significance of mtDNA research in shaping the future of biomedical sciences and highlights the importance of continued exploration into its intricate molecular code.
Identification of Key Features Pivotal to the Characteristics and Functions of Gut Bacteria Taxa through Machine Learning Methods.
Li Z, Ma Q, Li H … +6 more , Lu L, Chen L, Guo W, Feng K, Huang T, Cai YD
Curr Gene Ther · 2025 Jul · PMID 40671232 · Publisher ↗
BACKGROUND: Gut bacteria critically influence digestion, facilitate the breakdown of complex food substances, aid in essential nutrient synthesis, and contribute to immune system balance. However, current knowledge regar...
BACKGROUND: Gut bacteria critically influence digestion, facilitate the breakdown of complex food substances, aid in essential nutrient synthesis, and contribute to immune system balance. However, current knowledge regarding intestinal bacteria remains insufficient. OBJECTIVE: This study aims to discover essential differences for different intestinal bacteria. METHODS: This study was conducted by investigating a total of 1478 gut bacterial samples comprising 235 Actinobacteria, 447 Bacteroidetes, and 796 Firmicutes, by utilizing sophisticated machine learning algorithms. By building on the dataset provided by Chen et al., we engaged sophisticated machine learning techniques to further investigate and analyze the gut bacterial samples. Each sample in the dataset was described by 993 unique features associated with gut bacteria, including 342 features annotated by the Antibiotic Resistance Genes Database, Comprehensive Antibiotic Research Database, Kyoto Encyclopedia of Genes and Genomes, and Virulence Factors of Pathogenic Bacteria. We employed incremental feature selection methods within a computational framework to identify the optimal features for classification. RESULTS: Eleven feature ranking algorithms selected several key features as pivotal to the characteristics and functions of gut bacteria. These features appear to facilitate the identification of specific gut bacterial species. Additionally, we established quantitative rules for identifying Actinobacteria, Bacteroidetes, and Firmicutes. CONCLUSION: This research underscores the significant potential of machine learning in studying gut microbes and enhances our understanding of the multifaceted roles of gut bacteria.
Immunoinformatic Based Designing of Immune Boosting and Nonallergenic Multi-epitope Subunit Vaccine Against the Enterovirus D68.
Suleman M, Khan SU, Jabeen H … +5 more , Madkhali OA, Bakkari MA, Alsalhi A, Yassine HM, Crovella S
Curr Gene Ther · 2025 Jul · PMID 40660445 · Publisher ↗
INTRODUCTION: Enterovirus D68 (EV-D68) is a non-enveloped, positive-sense, singlestranded RNA virus known for causing severe respiratory illnesses and its association with acute flaccid myelitis (AFM) in children. Despit...
INTRODUCTION: Enterovirus D68 (EV-D68) is a non-enveloped, positive-sense, singlestranded RNA virus known for causing severe respiratory illnesses and its association with acute flaccid myelitis (AFM) in children. Despite its increasing public health significance, no vaccines or antiviral drugs are currently available for EV-D68. This study aimed to design an immune-boosting multi-epitope subunit vaccine against EV-D68 using advanced immunoinformatic and machine learning approaches. METHODS: Capsid proteins VP1, VP2, and VP3 of EV-D68 were screened for immunogenic HTL, CTL, and B-cell epitopes to develop a non-allergenic, highly immunogenic multi-epitope vaccine. Predicted epitopes were subjected to 3D structural modeling and molecular dynamics simulations to validate folding and structural stability. Molecular docking and immune simulation techniques were employed to evaluate vaccine-TLR3 interactions and predict immune responses, respectively. RESULTS: Molecular docking analysis revealed strong binding affinities between the vaccine constructs and the TLR3 receptor, with scores of -299 kcal/mol, -361 kcal/mol, -258 kcal/mol, and -312 kcal/mol for VP1, VP2, VP3, and combined vaccine-TLR3 complexes. Molecular dynamic simulation and dissociation constant analyses confirmed the strength of these interactions, with binding free energies ranging from -57.75 kcal/mol to -101.35 kcal/mol. Codon adaptation index (CAI) values of 0.96 and GC content of ~69% supported the high expression potential of the vaccine constructs. Immune simulations demonstrated robust immune responses characterized by elevated IgG, IgM, cytokines, and interleukins, along with effective antigen clearance. DISCUSSION: The strong molecular interactions with TLR3 and simulated immune responses suggest that the designed vaccines can activate both innate and adaptive immunity. The high CAI and GC values support their expression feasibility in , enhancing prospects for production. CONCLUSION: This study provides a strong foundation for the development of a safe and effective EV-D68 vaccine, showcasing the potential of computational vaccine design.
Review Deciphering the Anticancer Efficacy of Oroxylin A Targeting Dysregulated Oncogenes.
Pandey P, Ganesan S, Rajotiya S … +8 more , Devi S, Baldaniya L, Kumar MR, Lakhanpal S, Pandey S, Verma M, Ramniwas S, Khan F
Curr Gene Ther · 2025 Jul · PMID 40641012 · Publisher ↗
Flavonoids exhibit anti-tumor properties against many human cancer cells, indicating their potential as effective anticancer medicines. Oroxylin A (OrA) is a monoflavonoid molecule that shows significant promise against...
Flavonoids exhibit anti-tumor properties against many human cancer cells, indicating their potential as effective anticancer medicines. Oroxylin A (OrA) is a monoflavonoid molecule that shows significant promise against several types of cancer and possesses a substantial anticancer impact while causing minimal harm to normal tissue. Limited studies have provided a systematic review deciphering the role of oroxylin A in combating breast carcinoma. Hence, we thoroughly analyzed existing research to report various mechanism by which OrA impedes tumor advancement in breast carcinoma, including autophagy, cell cycle arrest, angiogenesis suppression, apoptosis, and glycolysis inhibition. We collected several significant research related to the anticancer potential of oroxylin A and demonstrated anticancerous potential of OrA and its specific mode of action in several human carcinomas. Additionally, we have also incorporated several studies to decipher the structure, bioavailability, and anti-breast cancer potential of Oroxylin A in breast cancer. Overall, this review supports the potential of oroxylin A for developing better anti breast cancer therapeutic approach.
Machine Learning-Driven PCDI Classifier for Invasive PitNETs.
Wang G, Yan S, Zhang L … +4 more , Lin L, Liu R, Han Y, Zhao Y
Curr Gene Ther · 2026 · PMID 40621753 · Publisher ↗
INTRODUCTION: Aggressive Pituitary Neuroendocrine Tumors (PitNETs) pose significant therapeutic challenges due to their invasive behavior and resistance to conventional therapies. Current prognostic markers lack the abil...
INTRODUCTION: Aggressive Pituitary Neuroendocrine Tumors (PitNETs) pose significant therapeutic challenges due to their invasive behavior and resistance to conventional therapies. Current prognostic markers lack the ability to capture molecular heterogeneity, necessitating novel biomarkers. Dysregulated Programmed Cell Death (PCD) pathways are implicated in tumorigenesis, but their prognostic relevance in invasive PitNETs remains unexplored. METHODS: GEO datasets (GSE51618, GSE169498, GSE260487) were analyzed to identify differential gene expression between noninvasive and invasive PitNETs. A curated panel of 1,548 PCDrelated genes was integrated. Machine learning (LASSO regression and SVM-RFE) was employed to construct a PCD-associated Index (PCDI). For validation, ROC analysis, immune infiltration assessment (CIBERSORT, TIMER, ssGSEA), and experimental validation via RT-qPCR were performed. RESULTS: The PCDI, comprising 11 genes (e.g., FGFR3, MAPK11, SLC7A11), distinguished invasive from noninvasive PitNETs with high accuracy. High-PCDI tumors exhibited enriched metabolic pathways and immune activation. Consensus clustering stratified PitNETs into two molecular subtypes (C1/C2), with C2 (high-PCDI) showing elevated immune scores and pathway activity. Experimental validation confirmed the differential expression of key genes in invasive tumors (*p<0.05). DISCUSSION: The PCDI outperforms traditional prognostic models by capturing PCD-immunemetabolic crosstalk. High-PCDI tumors demonstrate adaptive immune evasion despite an elevated checkpoint molecule expression, suggesting therapeutic potential for combined MAPK inhibitors and immunotherapy. Limitations include retrospective data and small validation cohorts. CONCLUSION: The PCDI provides a robust molecular framework for risk stratification and personalized therapy in invasive PitNETs. Future studies should validate its clinical utility and explore pancancer relevance.
Identification of Novel Biomarkers of Bacterial Lipopolysaccharides in Diabetic Nephropathy via Transcriptomics and Mendelian Randomization.
Ning Y, Wang J, Zhou X … +2 more , Wang G, Zhang L
Curr Gene Ther · 2026 · PMID 40611469 · Publisher ↗
BACKGROUND: Dysbiosis of Intestinal Flora Lipopolysaccharides (LPS) is implicated in Diabetic Nephropathy (DN), yet the underlying mechanisms remain unclear. This study aims to elucidate the causal relationship between b...
BACKGROUND: Dysbiosis of Intestinal Flora Lipopolysaccharides (LPS) is implicated in Diabetic Nephropathy (DN), yet the underlying mechanisms remain unclear. This study aims to elucidate the causal relationship between bacterial LPS and DN, with the goal of informing targeted therapeutic strategies. METHODS: DN datasets GSE30528 and GSE96804 were analyzed. Bacterial LPS-related genes (LPS-RGs) were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Differential expression analysis identified differentially expressed genes (DEGs), which were cross-referenced with LPS-RGs to derive DE-LPS-RGs. Mendelian randomization (MR) was applied to explore correlations between exposure factors and outcomes using GWAS data. miRNA-mRNA and TFmRNA regulatory networks were constructed using data from the TarBase and ENCODE databases, and potential therapeutic agents were identified through the DGIdb database. RESULTS: Seven DE-LPS-RGs were identified, with CD14 and LY86 selected as biomarkers. GSEA and GeneMANIA analyses indicated that these genes participate in signal transduction and chargelike receptor signaling pathways. The regulatory networks demonstrated that LY86 interacts with miRNA hsa-mir-26a-5p, while TF ELK1 regulates both CD14 and LY86. Additionally, CD14 was associated with three potential drugs: VB-201, IC14, and Lovastatin. CONCLUSION: CD14 and LY86 represent promising biomarkers for DN, offering new perspectives for its prediction, diagnosis, and therapeutic intervention.
The Genetic and Epidemiological Dimensions of Gallbladder Cancer: Toward Effective Therapeutic Strategies.
Siddiqui A, Sanyal S, Mukherjee D … +2 more , Dwivedi M, Dwivedi M
Curr Gene Ther · 2025 Jun · PMID 40600529 · Publisher ↗
Gallbladder Cancer (GBC) is a highly concerning malignancy, particularly prevalent in the Asian continent, attributed to irregularities in the bile tract. As of 2022, GLOBOCAN data ranks GBC as the 22nd most common cause...
Gallbladder Cancer (GBC) is a highly concerning malignancy, particularly prevalent in the Asian continent, attributed to irregularities in the bile tract. As of 2022, GLOBOCAN data ranks GBC as the 22nd most common cause of cancer-related mortality globally and the 6th among gastrointestinal cancers. According to recent World Cancer Research statistics, approximately 122,491 new cases of gallbladder cancer were reported by the end of 2022, ranking it 23rd among cancers in men and 20th in women worldwide. Towards the therapy of GBC, genetic studies have provided valuable insights into the molecular mechanisms driving GBC. Mutations in TP53, KRAS, ERBB2 (HER2), CDKN2A, and PIK3CA play crucial roles in tumor initiation and progression. Additionally, epigenetic modifications and aberrant signaling pathways, including Wnt/β-catenin, Notch, and PI3K/AKT/mTOR, have been implicated in GBC pathogenesis. Exploring these genetic alterations has led to targeted therapies, such as HER2 inhibitors (trastuzumab, pertuzumab) and immune checkpoint inhibitors, offering new treatment prospects. Further, current treatment approaches, including surgical resection, chemotherapy (gemcitabine-cisplatin), and radiation therapy, offer suboptimal outcomes in advanced stages of GBC. Despite its prevalence, effective therapeutic approaches and early-stage diagnostic methods remain elusive. This review provides a comprehensive overview of GBC, including its genetic mutations, epidemiology, risk factors, prevention, diagnosis, treatment options, and challenges. This work aims to offer valuable insights into the various factors directly or indirectly associated with GBC, which may assist in preparing an effective strategy against this growing malignancy.
Advancements in Targeted Therapies and Pharmacogenomics for Personalized Breast Cancer Treatment: The Role of Gene SNPs in Treatment Resistance.
Tripathi D, Davies NM, Rajinikanth PS … +1 more , Pandey P
Curr Gene Ther · 2025 Jun · PMID 40589001 · Publisher ↗
Breast cancer remains a prevalent and diverse disease, significantly contributing to cancer- related deaths among women worldwide. Recent advancements in molecular biology have paved the way for targeted therapies and ph...
Breast cancer remains a prevalent and diverse disease, significantly contributing to cancer- related deaths among women worldwide. Recent advancements in molecular biology have paved the way for targeted therapies and pharmacogenomics, which are crucial for developing personalized treatment strategies. This literature review synthesizes findings from recent studies on these approaches, emphasizing clinical trials, genomic profiling, and personalized medicine. It aims to focus on studies examining targeted treatments, such as human epidermal growth factor receptor- 2 (HER2) inhibitors and CDK4/6 inhibitors, alongside pharmacogenomic data that influence drug metabolism, efficacy, and toxicity. Additionally, it examines the role of gene SNPs (Single Nucleotide Polymorphisms) correlated with treatment resistance, which have emerged as key biomarkers affecting therapeutic outcomes in breast cancer. These SNPs, found in genes involved in drug metabolism and tumor progression, contribute to variability in treatment responses and resistance in specific subtypes. They encompass various breast cancer subtypes, including hormone receptorpositive (HR+), HER2-positive, and triple-negative breast cancer (TNBC). The targeted therapies, particularly HER2 inhibitors, have markedly improved outcomes for specific subtypes. Furthermore, pharmacogenomics personalizes treatment by identifying genetic variations that affect drug response, optimizing therapy selection, and minimizing adverse effects. Despite these advancements, drug resistance remains a significant challenge, highlighting the necessity for ongoing research in molecular diagnostics and innovative therapeutic combinations. The literature suggests that precision medicine, driven by genomic profiling, pharmacogenomic data, and single nucleotide polymorphisms (SNPs) analysis, is enhancing treatment efficacy for breast cancer patients. HER2- positive and HR+ patients have especially benefitted from these targeted therapies while emerging treatments are addressing the complexities of TNBC. Additionally, genetic testing, such as BRCA1/2 mutation screening, is vital for guiding treatment decisions. Targeted therapies and pharmacogenomics have revolutionized breast cancer treatment, providing more personalized and effective care. Nevertheless, overcoming drug resistance and expanding access to genomic testing are essential for future advancements in this field.
Bridging Mind and Gut: The Molecular Mechanisms of microRNA, Microbiota, and Cytokine Interactions in Depression.
Sharma H, Al Noman A, Ahmad I … +8 more , Tonni SD, Mim TJ, Afrose F, Sharma PD, Parvez A, Tamanna S, Al Azad M, Pathak R
Curr Gene Ther · 2026 · PMID 40589000 · Publisher ↗
Depression is a complex psychiatric disorder that arises from various underlying biological mechanisms. In this review, the role of microRNAs (miRNAs) in modulating gut microbiotacytokine communication and their potentia...
Depression is a complex psychiatric disorder that arises from various underlying biological mechanisms. In this review, the role of microRNAs (miRNAs) in modulating gut microbiotacytokine communication and their potential to unravel the pathophysiology of depression and develop novel therapeutic strategies are discussed. MiRNAs are small non-coding RNA molecules that have emerged as key regulators in the bidirectional signaling of the gut-brain axis by modulating gene expression and fine-tuning an intricate dialogue between the microbiota, immune system, and central nervous system. Results show how gut microbiota can shape miRNA expression in brain regions involved in mood regulation; conversely, evidence is accumulating, elucidating how miRNA perturbations can shape microbial ecology. Gut bacteria-derived short-chain fatty acids (SCFAs) fuel this nexus by exerting effects on neurogenesis, neurotransmitter synthesis, neuroinflammation, affective behavior alterations, and depressive-like phenotypes. Pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β are also known to be associated with depressive symptoms related to altered expression patterns of specific miRNAs across these disorders. This review exposes the novel potential biomarkers and therapeutic targets/strategies to develop innovative methods in the diagnosis and treatment of depression by exploring bidirectional relations among miRNAs, gut microbiota, and cytokines. The knowledge of these molecular networks and pathways has provided the opportunity for designing new-generation therapeutics such as phytobiotics, probiotics, psychobiotics, diet therapies, and nanomedicine based on miRNAs from a future perspective, which will revolutionize the management of mental disorders.
Therapeutic Effects of Mesenchymal Stem Cells Carrying Echovirus in Mouse Models of Breast Cancer.
Aminian F, Babaei N, Ghaleh HEG … +2 more , Khamisipour G, Farzanehpour M
Curr Gene Ther · 2025 Jun · PMID 40574395 · Publisher ↗
INTRODUCTION: Breast Cancer (BC) is treatable in early stages but has high mortality rates in advanced cases, highlighting the need for better treatment methods. Oncolytic Viruses (OVs) have emerged as a promising approa...
INTRODUCTION: Breast Cancer (BC) is treatable in early stages but has high mortality rates in advanced cases, highlighting the need for better treatment methods. Oncolytic Viruses (OVs) have emerged as a promising approach to specifically target and kill BC tumor cells, although their effectiveness is limited by the immune response. To overcome this challenge, researchers are investigating the use of cell carriers. This study aims to evaluate the effects of mesenchymal stem cells carrying Echovirus (MSCs-ECHO) in a BC mouse model. METHOD: The effectiveness of MSCs-ECHO was evaluated in a mouse model of BC induced by the subcutaneous injection of live 4T1 cells (1×104) in female Balb/c mice. Its effects were assessed using several parameters, including Tumor Size (TS), Survival Probability (SP), and indicators of immune system response, such as the Splenocyte Proliferation Index (SPI), Nitric Oxide (NO), Lactate Dehydrogenase (LDH), and cytokines (IL-4, IL-10, IFN-γ, and TGF-β) in the supernatant of splenocytes. RESULTS: Our findings revealed that treatment with MSCs-ECHO significantly increased SP, SPI, LDH, NO, and IFN-γ levels, while reducing TS, TGF-β, IL-4, and IL-10 levels in treated mice compared to the control group. Additionally, MSCs-ECHO demonstrated superior therapeutic effects compared to treatment with cell-free virus. CONCLUSION: These findings indicate that ECHO treatment may represent a promising therapeutic approach for BC. Based on the results of the present study, the utilization of MSCs as carriers for OV appears to be a viable complementary strategy in the management of BC.
Novel Perspective of Regulating P53/Bcl2/Caspase-3 via In vitro Targeted AFP Gene Knocks Out in HepG2 Cells Using CRISPR/Cas9 Editing Tool.
Khorshed F, Medhat AM, Hamdy GM … +4 more , El-Dabaa E, Hammad H, Abd Elhameed HAH, Saber M
Curr Gene Ther · 2025 Jun · PMID 40511828 · Publisher ↗
INTRODUCTION: Hepatocellular carcinoma (HCC) is a major health burden worldwide, with a persistent need for molecular target drugs. Alpha-fetoprotein (AFP) is a major concern during HCC, as it has an incompletely solved...
INTRODUCTION: Hepatocellular carcinoma (HCC) is a major health burden worldwide, with a persistent need for molecular target drugs. Alpha-fetoprotein (AFP) is a major concern during HCC, as it has an incompletely solved action. CRISPR/Cas9 is a gene editing tool that aids in cancer treatment research; thus, this study evaluated the effect of in vitro knockout of AFP on HCC using CRISPR/Cas9 technique. METHODS: Two sgRNAs targeting specific sites in AFP exon 2 were separately cloned to the mammalian expression vector pSpCas9 (BB)-2a-GFP (PX458). HepG2 cells were transfected with CRISPR constructs I and II, and a pool of the two constructs (M) for 6 -, 24- and 39 hours using liopfectamine3000. AFP editing was evaluated regarding genomic DNA sequence, RNA, and protein expression levels. In addition, the effect of AFP knocking out on HepG2 viability, and apoptotic genes mRNA and protein expression levels were evaluated using crystal violet assay, real-time PCR, and western blot analysis respectively. RESULTS: The results revealed efficient delivery of the AFP/CRISPR constructs to HepG2 cells. Insertion and deletion mutations introduced to the AFP genomic sequence were analyzed using TIDE software analysis and the Expasy translation tool. The viability of the HepG2 cells was reduced 39 hours post-transfection with significant modulation in the expression of the apoptotic markers P53, BAX, Bcl2, and caspase-3. CONCLUSION: This study succeeded in developing AFP/CRISPR constructs that could disrupt the AFP genomic sequence, reduce its expression, and restore the activity of cell-specific apoptotic factors, demonstrating the potential inhibitory effect of AFP downregulation on HCC progression.
Next-Generation Nucleic Acid Delivery: A Review of Nanobiosystem Design and Applications.
Parashar AK, Hardenia A, Dwivedi SK … +2 more , Saraogi GK, Hardenia S
Curr Gene Ther · 2025 May · PMID 40444614 · Publisher ↗
The increasing approval of nucleic acid therapeutics has led to a significant advancement in medicines, demonstrating their potential to revolutionize the prevention and treatment of numerous diseases. However, challenge...
The increasing approval of nucleic acid therapeutics has led to a significant advancement in medicines, demonstrating their potential to revolutionize the prevention and treatment of numerous diseases. However, challenges like nuclease degradation and difficult cellular delivery hinder their use as therapeutic agents. The rising demand for precise gene therapy delivery has positioned nanobiosystems as a groundbreaking solution, with their customizable properties enabling targeted and efficient delivery. Nucleic Acid therapeutics, encompassing antisense DNA, mRNA, small interfering RNA (siRNA), and microRNA (miRNA), have been rigorously investigated for their capacity to modulate gene expression. Notably, integrating these gene therapies with nanoscale delivery platforms has significantly broadened their scope, facilitating sophisticated advancements in bioanalysis, gene silencing, protein replacement therapies, and the development of vaccines. This review provides a thorough review of recent advancements in nanobiosystems for therapeutic nucleic acid delivery. We explore the unique characteristics of various nanobiosystems, including gene therapy-based delivery, nanoparticles, stimuli-responsive systems, smart nanocarriers, and extracellular vesicle-based delivery. We offer a detailed overview of their applications in nucleic acid delivery. Furthermore, we address biological barriers and strategies for the therapeutic delivery of nucleic acids. Ultimately, this review provides critical insights into the strategic development of nextgeneration delivery vectors for nucleic acid therapeutics.
Targeting Extrachromosomal DNA (ecDNA) in Cancer: A New Era of CHK1 Inhibition and Personalized Treatments.
Komal, Singh L, Ganti SS
Curr Gene Ther · 2026 · PMID 40444613 · Publisher ↗
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Elucidating the Predominant Role of AEBP1 in Different Types of Cancers with a Focus on Glioblastoma Progression - A Review.
Kaviyaprabha R, Muthusami S, Miji TV … +2 more , Arulselvan P, Bharathi M
Curr Gene Ther · 2026 · PMID 40375702 · Publisher ↗
INTRODUCTION: Glioblastoma multiforme (GBM) is a highly deleterious lesion with an increased recurrence rate even after radiotherapy and chemotherapy. In this context, additional biomarkers are needed to curb chemoresist...
INTRODUCTION: Glioblastoma multiforme (GBM) is a highly deleterious lesion with an increased recurrence rate even after radiotherapy and chemotherapy. In this context, additional biomarkers are needed to curb chemoresistance. Computational approaches help us process the RNA-seq and identify the Differentially Expressed Genes (DEGs) in tumors and adjacent normal regions to identify the diagnostic and therapeutic biomarkers. METHODS AND MATERIALS: In this study, we extensively reviewed the role of AEBP1 in different types of cancer, highlighting its significance as a novel target to prevent collagen deposition. Specifically, the underlying mechanisms of AEBP1 in Glioblastoma were analyzed extensively using computational approaches that include Gene Expression Omnibus (GEO), GEPIA to obtain the TCGA-GBM dataset, and Glioma-BioDP to identify the survival rate in the context of AEBP1 expression associated with patients' age. Meanwhile, Tumor Immune Single-cell Hub 2 was implemented to identify the expression of AEBP1 in immunologically lineaged, cancerous, and stromal cells. In addition to that, the miRNA regulation associated with the AEBP1 expression was predicted by implementing NetworkAnalyst, TarBase v8.0, and CancerMIRNome. We identified the DEGs by examining the GSE121723, GSE184643, and GSE14824 datasets with P-values ≤ 0.05 as statistically significant. Furthermore, we predicted and analyzed the highly expressed genes and identified the survival rate, which significantly stated that the overexpression of AEBP1 was associated with decreased survival rates in GBM patients. The Protein-Protein Interaction network was constructed to identify the correlated gene expression. RESULTS AND DISCUSSION: We identified 3695, 37001, and 8855 significantly differentially expressed genes (DEGs). The DEGs were filtered by applying a log2 fold-change cut-off of ≥2.0. Finally, 139 common genes were mapped with the identified DEGs (1338 genes) and SDEGs (500 genes) estimated from the TCGA-GBM dataset. The analysis revealed that 155 genes are commonly upregulated, and survival analyses were performed that described the AEBP1 significantly reduced the GBM patients' survival rate among other genes. The constructed PPI network and correlated expression analysis associated with the AEBP1 expression revealed that COL6A2 and THBS2 might play a significant role in the GBM stage advancements by depositing collagens in the matrix environment. Also, the miRNA analysis revealed that the hsa-miR-128-3p and hsa-miR-512-3p could be targeted as a miRNA marker gene to prevent the GBM progression associated with the AEBP1 expression. CONCLUSION: AEBP1 is a multi-cancer drug target, underscoring its diagnostic and prognostic value in different types of cancer preventive medicine. It influences tumor growth, metastasis, and immune evasion in cancers like adrenocortical, oral, breast, bladder, gastric, colon, and ovarian by activating the NF-κB pathway and disrupting tumor suppressors. Our findings additionally identified AEBP1 as a key regulator in glioblastoma (GBM) progression, with its overexpression (log2FC = 8.207; P ≤ 0.05) linked to reduced survival (HR = 2.1; P = 4.9e). Targeting AEBP1 via TGFβs and its receptors could inhibit the collagen-depositing gene COL6A2 and THBS2, a key TME modulator. Further, the hsa-miR-128-3p (AUC = 0.94) could be a potential therapeutic target to prevent the expression of AEBP1. Following an extensive review and in-depth discussion, our investigation presents a potentially promising avenue to develop small drug-like molecules and monoclonal antibodies against AEBP1 expression for ameliorating patient survival rates.
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